Sodium Bicarbonate → 2-Methyl-5-oxo-4-{3-[6-(propan-2-yloxy)pyridin-3-yl}-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro-[3,4-b]pyridine-3-carbonitrile

HRID 408558Notes

Reaction equation

HRID 408558 reaction equation
Br[C:2]1[C:10]2[C:5](=[CH:6][CH:7]=[C:8]([CH:11]3[C:16]([C:17]#[N:18])=[C:15]([CH3:19])[NH:14][C:13]4[CH2:20][O:21][C:22](=[O:23])[C:12]3=4)[CH:9]=2)[NH:4][N:3]=1.[CH3:24][CH:25]([O:27][C:28]1[N:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1)[CH3:26].C(=O)(O)[O-].[Na+]>O1CCOCC1.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:19][C:15]1[NH:14][C:13]2[CH2:20][O:21][C:22](=[O:23])[C:12]=2[CH:11]([C:8]2[CH:9]=[C:10]3[C:5](=[CH:6][CH:7]=2)[NH:4][N:3]=[C:2]3[C:31]2[CH:32]=[N:33][C:28]([O:27][CH:25]([CH3:26])[CH3:24])=[CH:29][CH:30]=2)[C:16]=1[C:17]#[N:18]

Participants

6

Reactant 3

HCID 516892Sodium BicarbonateHCID 44754864[6-(Propan-2-yloxy)pyridin-3-yl]boronic acidHCID 178428406HCID 178428406, compound

Product 1

HCID 469112702-Methyl-5-oxo-4-{3-[6-(propan-2-yloxy)pyridin-3-yl}-1H-indazol-5-yl]-1,4,5,7-tetrahydrofuro-[3,4-b]pyridine-3-carbonitrileYield 19.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a degassed solution of 120 mg (0.323 mmol) 4-(3-bromo-1H-indazol-5-yl)-2-methyl-5-oxo-1,4,5,7-tetrahydrofuro[3,4-b]pyridine-3-carbonitrile (Example 24) and 70.2 mg (0.388 mmol) [6-(propan-2-yloxy)pyridin-3-yl]boronic acid in anhydrous 1,4-dioxane (3.5 ml) were added under inert gas atmosphere 37.4 mg (0.032 mmol) tetrakis(triphenylphosphine)palladium(0) and aqueous sodium bicarbonate solution (2 M, 0.77 ml). The resulting mixture was stirred at 100° C. for 12 h. After cooling to room temperature and concentration under reduced pressure, the remaining solid was dissolved in ethyl acetate (20 ml). The solution was subsequently washed with water and brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v) to yield the title compound as a white solid (27 mg, 19% of th.).

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationconcentration under reduced pressure
  3. dissolutionthe remaining solid was dissolved in ethyl acetate (20 ml)
  4. washThe solution was subsequently washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe crude product was purified by preparative RP-HPLC (acetonitrile/water gradient, final mixture 95:5 v/v)

Sources & evidence

ORD record
ord-b9d2cb5b011247199a4fa4f996baa603
Source dataset
uspto-grants-2014_06
Patent number
US08759341B2

Reaction notes

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